{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:48:15Z","timestamp":1760240895202,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T00:00:00Z","timestamp":1571875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FIPE - Fundo de incentivo a Pesquisa do Hospital de Clinicas de Porto Alegre","award":["13-0360"],"award-info":[{"award-number":["13-0360"]}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["141840\/2017-0"],"award-info":[{"award-number":["141840\/2017-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome that results from dominant loss-of-function mutations mainly in the NF1 gene. Large rearrangements are present in 5\u201310% of affected patients, generally encompass NF1 neighboring genes, and are correlated with a more severe NF1 phenotype. Evident genotype\u2013phenotype correlations and the importance of the co-deleted genes are difficult to establish. In our study we employed an evolutionary approach to provide further insights into the understanding of the fundamental function of genes that are co-deleted in subjects with NF1 microdeletions. Our goal was to access the ortholog and paralog relationship of these genes in primates and verify if purifying or positive selection are acting on these genes. Fourteen genes were analyzed in twelve mammalian species. Of these, four and ten genes showed positive selection and purifying selection, respectively. The protein, RNF135, showed three sites under positive selection at the RING finger domain, which may have been selected to increase efficiency in ubiquitination routes in primates. The phylogenetic analysis suggests distinct evolutionary constraint between the analyzed genes. With these analyses, we hope to help clarify the correlation of the co-deletion of these genes and the more severe phenotype of NF1.<\/jats:p>","DOI":"10.3390\/genes10110839","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T04:41:27Z","timestamp":1571978487000},"page":"839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Role of Co-Deleted Genes in Neurofibromatosis Type 1 Microdeletions: An Evolutive Approach"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9833-9058","authenticated-orcid":false,"given":"Larissa","family":"Brussa Reis","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Medicina Gen\u00f4mica, Centro de Pesquisa Experimental, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre, Rio Grande do Sul 90035-903, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Gen\u00e9tica e Biologia Molecular, Departamento de Gen\u00e9tica, UFRGS, Porto Alegre, Rio Grande do Sul 91501-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreia Carina","family":"Turchetto-Zolet","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Gen\u00e9tica e Biologia Molecular, Departamento de Gen\u00e9tica, UFRGS, Porto Alegre, Rio Grande do Sul 91501-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maievi","family":"Fonini","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Medicina Gen\u00f4mica, Centro de Pesquisa Experimental, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre, Rio Grande do Sul 90035-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Ashton-Prolla","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Medicina Gen\u00f4mica, Centro de Pesquisa Experimental, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre, Rio Grande do Sul 90035-903, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Gen\u00e9tica e Biologia Molecular, Departamento de Gen\u00e9tica, UFRGS, Porto Alegre, Rio Grande do Sul 91501-970, Brazil"},{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica do Hospital de Cl\u00ednicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul 90035-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e9via","family":"Rosset","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Medicina Gen\u00f4mica, Centro de Pesquisa Experimental, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre, Rio Grande do Sul 90035-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/oxfordjournals.aje.a010118","article-title":"NF1 gene and neurofibromatosis 1","volume":"151","author":"Rasmussen","year":"2000","journal-title":"Am. 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